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Biomedical subjects

A Raynaud-Simon

Publications and source records attributed to A Raynaud-Simon.

8 recordsLinked to original sources

Levels of plasma insulin-like growth factor I (IGF I), IGF II, IGF binding proteins, type 1 IGF receptor and growth hormone binding protein in community-dwelling elderly subjects with no malnutrition and no inflammation.

Plasma samples from community-dwelling subjects aged 65 to 92 presenting no malnutrition and no inflammation (as assessed by albumin, transthyretin, CRP, and orosomucoid levels and BMI) were compared to those of healthy controls aged 20 to 65 to determine the effect of aging on the IGF system. Concentrations of IGF I, IGF II and IGFBP3 significantly decreased, and those of GHBP slightly increased with age from 20 to 92 years (n=327 r=-0.64 p<0.0001; n=45 r=-0.44 p<0.003; n=91 r=-0.23 p<0.03 and n=61 r=0.26; p<0.05 respectively). Western immunoblotting showed that the proteolysis of IGFBP3 was not significantly different in elderly and younger subjects. The affinity of the IGF type 1 receptor for IGF I was moderately lower (Ki=0.56 0.2 vs 0.33 0.1, nM respectively; p<0.005) and the number of binding sites was moderately higher (10.4 1.5 vs 8.1 1.9 binding sites/cell, respectively; p<0.03) in the elderly than in the younger adults. Our results suggest that the age-related decline in plasma levels of IGF I, IGF II and IGFBP3 occurs independently from malnutrition and inflammation processes. GHBP plasma levels, which reflect the number of GH receptors at the level of the liver, do not decline in our malnutrition-free elderly population, and thus are not involved in the decline of IGF I plasma levels with age. In the elderly, affinity and number of type 1 IGF receptor were close to those of younger subjects; the decline in IGF I plasma levels may account for the small rise in the number of type 1 IGF receptors binding sites per cell.

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Orosomucoid: a mortality risk factor in elderly people living in the community?

AIM: We explored the value of variables relating to inflammation and nutrition as a prognostic factors for mortality in an elderly community-dwelling population. METHODS: We measured plasma levels of orosomucoid, C-reactive protein (CRP), albumin, and transthyretin, and the body mass index (BMI) of 245 subjects aged 65 to 95 living in the community (PAQUID study). The risk of death was analyzed two, four and six years after blood sampling by use of the Cox proportional hazards model with delayed entry. A survival curve was generated by the Kaplan-Meier method. RESULTS: Multivariate analysis--including sex, BMI, and plasma levels of albumin, transthyretin orosomucoid and CRP levels--showed that orosomucoid in the highest quartile (>0.88 g/L) was the strongest predictor of mortality two years after blood sampling [relative risk (RR)=7.4; 95% interval confidence (IC) 2.2-24.6; P<0.1]; the association remained significant four and six years after blood sampling [RR=2.5; 95%IC 1.2-5.2 and RR=1.9; 95%IC 1.0-3.4 respectively, P<0.05]. Orosomucoid levels above 1 g/L (the most accurate threshold for prediction of mortality) were associated with a strong increase in the risk of death two years [RR=12.3; 95%IC 4.3-35.0; P<0.001], four years [RR=6.9; 95%IC 3.3-14.7; P<0.001], and six years [RR=4.4; 95%IC 2.3-8.5; P<0.001) after blood sampling. CONCLUSION: These results further underline the association between systemic inflammation and mortality. They may help us to identify of high-risk subpopulations of elderly subjects so we can employ prevention strategies.

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IGF-I, IGF-I-binding proteins and GH-binding protein in malnourished elderly patients with inflammation receiving refeeding therapy.

OBJECTIVE: To investigate the mechanisms determining the success or failure of refeeding therapy in malnourished elderly patients with inflammation by studying changes in plasma IGF-I, GH-binding protein (GHBP) and IGF-binding protein (IGFBP) levels and IGFBP-3 proteolysis. DESIGN AND METHODS: We studied 15 severely malnourished hospitalized elderly patients. Weight, food intake, plasma albumin, transthyretin, C-reactive protein (CRP), orosomucoid, interleukin-6 (IL-6), IGF-I, intact and proteolytically degraded IGFBP-3 and GHBP levels were determined on admission and during refeeding therapy designed to increase food intake to 40 kcal/kg body weight per day (15% protein). RESULTS: Plasma IGF-I, IGFBP-3 and GHBP levels were significantly low for age on admission in all malnourished elderly patients. They increased in nine patients as nutritional status improved (albuminemia >30 g/l; transthyretinemia >200 mg/l or weight gain >5% of initial body weight) and levels of inflammation markers decreased (group 1). In contrast, plasma IGF-I, IGFBP-3 and GHBP levels remained low in six patients in whom nutritional status failed to improve and levels of inflammation markers increased (group 2). IGF-I showed greater variations than IGFBP-3 or GHBP with respect to nutritional status. High plasma CRP and IL-6 levels were associated with high levels of IGFBP-3 proteolysis. CONCLUSION: Efficient refeeding therapy was associated with a significant increase in IGF-I plasma levels. In patients with severe and persistent inflammation, high levels of proteolysis of IGFBP-3 may have contributed to the low plasma IGF-I levels, persistence of hypercatabolism and lack of improvement in nutritional status.

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[Malnutrition in the elderly. Clinical consequences].

UNLABELLED: A COMMON PROBLEM: Undernutrition occurs when nutrient intake does not meet nutritional needs. Selective food intake induced micronutrient deficits (moderate undernutrition) and can later lead to protein calorie malnutrition (PCM). PCM is often discovered during acute illness (increased nutritional needs). PCM is observed in 30 to 50% of the institutionalized population and in 2-4% of the elderly living at home. Micronutrient deficits are far more frequent and concern 4 million elderly persons in France. AGE-RELATED CHANGES: Decreased smell and taste capacities and the inability to modify eating habits in stress conditions are mainly responsible for low food intake. Low intake leads to immunodeficiency, and subsequent frailty. Any intercurrent illness aggravates both undernutrition and immunodeficiency, creating a disease-to-disease spiral (undernutrition-immunodeficiency) that is difficult to inverse. SIGNS OF PCM: Early signs of protein-calorie malnutrition are nonspecific: fatigue, apathy, decline in muscle strength. It is important to diagnose undernutrition at this stage before more specific symptoms develop: anorexia, weight loss, infection. Metabolic disorders occur at a later stage, generally during an acute illness, leading to overt PCM with perturbed glucose metabolism, recurrent infection, dehydration, impaired wound healing and calcium bone loss. The length of refeeding therapy depends on the intensity of the clinical signs, weight loss, dehydration, glucose metabolism disorder and/or on the severity of clinical complications such as infection or bone fractures. PRACTICAL ATTITUDE: Under nutrition must be recognized early at the stage of nonspecific clinical expression. Practitioners must be constantly aware of the risk of undernutrition and search for nonspecific signs in the elderly.

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Sarcopenia, hypermetabolism, and aging.

Sarcopenia is a constant in aging. Observed over long periods, it can reach 1% per year. But it is such a tenuous phenomenon that it cannot be observed over short periods at steady state. The aging phenomenon mainly hits fibers, Type II but on aged muscle thin, normal, and hypertrophic fibers cohabit with sclerosis and fat increases. Sarcopenia is difficult to study, due to the lack of simple clinical, biochemical, or imaging measures. Anthropometric data are largely dependent on water content. DEXA gives better information on appendicular muscle loss. Measures of strength analyze functional outcomes of sarcopenia. Sarcopenia appears largely multifactorial. Hormonal changes, e.g., drop in growth hormone, menopause, and andropause, explain impaired protein synthesis. Disuse (sedentary, bed rest) may explain chronical protein lysis. But the main factors for muscle lysis imply life events and occurring diseases. Cytokines (IL6, TNF alpha) and stress hormones (cortisol) induce quick protein lysis in muscle. Rapid and intensive successive aggressions during life cannot be compensated by slowed synthesis. Harmful consequences of sarcopenia explain many disabilities of old age: loss of strength, inducing itself loss of mobility, falls, equilibrium disorders, poor ADL: loss of nutritional reserves (protein and glycogen) impairing capacities of immune response. Muscle loss spoils vital functions as respiration. Treatment remains rather limited to resistance exercise. Although, these results are thin, they are the only ones to be validated in all the elderly even the frail or the old. However it is not efficient during the evolution of an inflammatory process. The powerful action of cytokine and cortisol on muscular hypermetabolism must be incited for early treatment of any infectious or inflammatory event. Nutritional supplementation has no efficiency in the absence of malnutrition and without exercise. Although mobility impairments mainly due to sarcopenia are the first cause of disablement in the elderly, we lack information on etiology, evolution, and measurement of sarcopenia. We also lack controlled therapeutical studies.

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Plasma insulin-like growth factor I levels in the elderly: relation to plasma dehydroepiandrosterone sulfate levels, nutritional status, health and mortality.

BACKGROUND: Insulin-like growth factor I (IGF-I) has beneficial metabolic effects. Because plasma IGF-I levels have been reported to be enhanced by dehydroepiandrosterone (DHEA) administration, it has been suggested that the IGF-I may be implicated in some of the reported associations between low DHEA sulfate (DHEAS) levels and impaired health measures in elderly subjects. The nutritional status, which also regulates plasma IGF-I levels, is also an important determinant of health outcome. OBJECTIVE: We sought to investigate the associations between plasma IGF-I levels and plasma DHEAS levels, nutritional status, health, and mortality in the elderly. METHODS: In 256 community-dwelling subjects aged 65-101 years, enrolled in the Paquid study, a health questionnaire was used to acertain their functional disabilities, any history of medical disorders, self-perceived health, depressive symptoms, and their cognitive function. Biological measurements included levels of plasma IGF-I, albumin, transthyretin, and DHEAS. Mortality data were available for 6 years following blood sampling. RESULTS: In this elderly population with no impairment in nutritional status, the plasma IGF-I levels decreased significantly with age (p = 0.02). The plasma IGF-I levels correlated positively with those of transthyretin (p = 0.0001). IGF-I also correlated with DHEAS (p = 0.04), but the correlation did not remain significant after adjustment for age. As opposed to SDHEA, the plasma IGF-I levels did not correlate with the results from the health questionnaire. The baseline IGF-I values in the highest tertile were associated with a higher risk of short-term mortality than those in the lowest tertile (RR = 8.4 at 2 years, p = 0.007). CONCLUSIONS: Our results suggest that IGF-I is not connected with the association between low plasma DHEAS levels and the impaired results from the health questionnaire. The relationship between plasma IGF-I highest levels and mortality should be further explored.

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